Under the label of Episodic syndromes that may be associated with migraine (code 1.6), the most recent headache classification considers several conditions involving GI symptoms which can manifest in patients who also have migraine without and with aura or are at increased likelihood of developing either of these headache forms. Typically indicated as conditions occurring in childhood, they may also occur in adults. Recurrent gastrointestinal disturbance (code 1.6.1.) is described as “Recurrent episodic attacks of abdominal pain and/or discomfort, nausea and/or vomiting, occurring infrequently, chronically or at predictable intervals, that may be associated with migraine”. The diagnostic criteria require at least five attacks with distinct episodes of abdominal pain and/or discomfort and/or nausea and/or vomiting; normal gastrointestinal examination and evaluation; absence of any other disorder which could account for these symptoms. A first subcategory is represented by Cyclic vomiting syndrome (CVS) (code 1.6.1.1), described as “Recurrent episodic attacks of intense nausea and vomiting, usually stereotypical in the individual and with predictable timing of episodes. Attacks may be associated with pallor and lethargy. There is complete resolution of symptoms between attacks”. The cyclic nature is the hallmark, and is predictable; episodes usually start at the same time of day, have similar duration, intensity and type of associated symptoms and prodromal phenomena are often present. The attacks are very disabling. Triggering factors are often identifiable, such as menstruation, lack of sleep, certain foods, physical exertion and stress. The clinical features of this syndrome resemble those found in association with migraine headaches, and multiple threads of research over the last years have suggested that cyclic vomiting syndrome is a condition related to migraine. Typically occurring in childhood, CVS also manifests in adults, though its prevalence in this population is at present unknown [38, 77]. Calhoun and Pruitt (2014) [11] performed an analysis of the literature, based on which they concluded that CVS likely represents a disorder on the migraine spectrum because CVS in adults is not only highly comorbid with migraine, but it responds to migraine preventives and in some cases to injectable sumatriptan even in the absence of headache. A second subcategory of recurrent gastrointestinal disturbance is abdominal migraine (code 1.6.1.2), described as “An idiopathic disorder seen mainly in children as recurrent attacks of moderate to severe midline abdominal pain, associated with vasomotor symptoms, nausea and vomiting, lasting 2–72 h and with normality between episodes. Headache does not occur during these episodes”. Pain of abdominal migraine is severe enough to interfere with normal daily activities. In young children, the presence of headache is often overlooked, and in the headache classification, it is underlined how a careful history of presence or absence of headache must be taken in these cases, and, if headache or head pain during attacks is identified, a diagnosis of migraine without aura should be considered. Most children with abdominal migraine will develop migraine headache later in life [37].

The frequent association of headache, particularly migraine, with symptoms consistent with a diagnosis of functional gastrointestinal diseases (FGIDs) is revealed by numerous clinical observations and epidemiological studies [1, 12, 16, 48, 56]. The study by Aamodt, in particular (population-based, cross-sectional) [1], showed a higher prevalence of headache, including migraine, in subjects complaining of reflux symptoms, diarrhoea, constipation or nausea vs subjects not presenting with these symptoms. The paper by Cole et al. (2006) [16], reporting a large cohort study involving 97,593 patients with irritable bowel syndrome (IBS), showed a higher prevalence of migraine (6 %) vs healthy controls (2.2 %). However, a study of dyspeptic patients referred for upper gastrointestinal endoscopy failed to show a difference in migraine prevalence in patients with reflux-like/ulcer-like dyspepsia vs healthy controls, being higher only among those with dysmotility-like dyspepsia [56].

In 2011, Lackner et al. [49] published a study in which they evaluated 175 IBS patients (diagnosis according to Rome III criteria) (median age, 41 years; 78 % women), referred to two specialty care clinics, for IBS symptom severity, comorbidities, psychiatric profile, abdominal pain intensity, health status and quality of life. There was an average of 5 comorbidities (1 mental, 4 physical) in IBS patients, the worst QOL occurring in those with more comorbidities. Comorbidity type was strongly associated with illness burden indicators. Tension-type headache was among the most frequent comorbidities, consistently associated with greater illness and symptom burdens (QOL, mental and physical function, distress, more severe symptoms of IBS, pain). The authors conclude that comorbidities are common among patients with IBS and are associated with distress and reduced QOL. Specific comorbidities (among which tension-type headache) are associated with more severe symptoms of IBS.

More recently, Park et al. [62] evaluated the prevalence of functional symptoms (using Rome III criteria to classify FGID) in a prospective, systematically acquired cohort of migraine patients attending a teaching hospital in Korea. They aimed to clarify the relationship among these concomitant functional symptoms, psychological comorbidity and headache-related disability. In a prospective regimen, 109 migraine sufferers recruited from a headache clinic at a teaching hospital completed a self-administered survey that collected information on headache characteristics, functional gastrointestinal symptoms, anxiety, depression and headache-related disability. A total of 71 % of the patients met the Rome III criteria for at least one FGID. In patients with FGID, irritable bowel syndrome was the most common diagnosis (40.4 %), followed by nausea and vomiting syndrome (24.8 %) and functional dyspepsia (23.9 %). A specific difference among IBS subtypes in relation to the association with migraine was also found, with IBS-M (mixed, diarrhoea-constipation) being the most prevalent in migraine. Depression and anxiety scores were significantly higher in patients meeting the criteria for any FGID. The number of the symptoms consistent with FGID in individual patients correlated positively with depression and anxiety.

The authors conclude that FGID symptoms defined by the Rome III criteria are highly prevalent in migraine and that these symptoms correlate with psychological comorbidities, such as depression and anxiety.

The mechanisms beyond the frequent association between migraine and FGIDs still need to be clarified. Possible pathways common to both may involve the brain-gut axis, neuro-immunity and neuroendocrine interactions [58, 66]. Altered serotonin signalling is also a possibility together with a genetic predisposition, since IBS and migraine show strong familial aggregation [23, 24]. Polymorphisms in the promoter region of the serotonin reuptake transporter (SERT) gene (SERT deletion/deletion genotype) are associated with IBS, especially diarrhoea-predominant IBS [63], and SERT gene polymorphism of the variable number of tandem repeats is associated with migraine [64].

Among the various pathogenetic hypothesis for the comorbidity, however, the role of sensitization mechanisms seems particularly plausible. Although the pathophysiology of functional abdominal pain is incompletely understood, in fact, it has been postulated that peripheral sensitisation of visceral afferents, central sensitisation of the spinal dorsal horn and aberrancies within descending modulatory systems may have an important role [22]. Most patients with IBS present a generalized increase in pain sensitivity, the typical hallmark of central sensitization, similarly to patients with migraine and tension-type headache, especially with a high frequency of attacks/chronic [10, 59, 92].

The comorbidity between functional gastrointestinal disorders and headache has implications for therapy. The management of patients with functional abdominal pain requires a tailored multidisciplinary approach in a supportive and empathetic environment in order to develop an effective therapeutic relationship. In the opinion of Farmer and Aziz [22], patient education directed towards an explanation of the pathophysiology of functional abdominal pain is a prerequisite step and provides the rationale for the introduction of interventions. A similar approach is also indispensable for headache patients as a premise towards the therapeutic measures. For functional visceral pain, interventions can usefully be categorized into general measures, pharmacotherapy, psychological interventions and “step-up” treatments. Pharmacotherapeutic/step-up options include tricyclic antidepressants, serotonin noradrenergic reuptake inhibitors and the gabapentinoids, the same class compounds used for prophylaxis in headache. Psychological treatments for FGIDs include cognitive behavioural therapy, recommended also in headache, and hypnotherapy. An integrated approach to both the headache problem and visceral pain condition in these patients is therefore highly advisable.